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PPARδ is required for exercise to attenuate endoplasmic reticulum stress and endothelial dysfunction in diabetic mice
Wai San Cheang1,2; Wing Tak Wong3; Lei Zhao1; Jian Xu1; Li Wang1; Chi Wai Lau1; Zhen Yu Chen3; Ronald Ching Wan Ma4; Aimin Xu5; Nanping Wang6; Xiao Yu Tian1; Yu Huang1
2017
Source PublicationDIABETES
ISSN0012-1797
Volume66Issue:2Pages:519-528
Abstract

Physical activity has profound benefits on health, especially on cardiometabolic wellness. Experiments in rodents with trained exercise have shown that exercise improves vascular function and reduces vascular inflammation by modulating the balance between nitric oxide (NO) and oxidative stress. However, the upstream regulator of exercise-induced vascular benefits is unclear. We aimed to investigate the involvement of peroxisome proliferator–activated receptor δ (PPARδ) in exercise-induced vascular functional improvement. We show that PPARδ is a crucial mediator for exercise to exert a beneficial effect on the vascular endothelium in diabetic mice. In db/db mice and high-fat diet–induced obese mice, 4 weeks of treadmill exercise restored endothelium-dependent vasodilation of aortas and flow-mediated vasodilation in mesenteric resistance arteries, whereas genetic ablation of Ppard abolished such improvements. Exercise induces AMPK activation and subsequent PPARδ activation, which help to reduce endoplasmic reticulum (ER) and oxidative stress, thus increasing NO bioavailability in endothelial cells and vascular tissues. Chemical chaperones 4-phenylbutyric acid and tauroursodeoxycholic acid decrease ER stress and protect against endothelial dysfunction in diabetic mice. The results demonstrate that PPARδ-mediated inhibition of ER stress contributes to the vascular benefits of exercise and provides potentially effective targets for treating diabetic vasculopathy.

DOIhttps://doi.org/10.2337/db15-1657
Indexed BySCI
Language英语
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000392691000028
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Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXiao Yu Tian; Yu Huang
Affiliation1.Institute of Vascular Medicine, Shenzhen Research Institute, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong
2.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau
3.School of Life Sciences, Chinese University of Hong Kong, Hong Kong
4.Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong
5.Departments of Medicine and Pharmacology and Pharmacy, State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong
6.Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wai San Cheang,Wing Tak Wong,Lei Zhao,et al. PPARδ is required for exercise to attenuate endoplasmic reticulum stress and endothelial dysfunction in diabetic mice[J]. DIABETES,2017,66(2):519-528.
APA Wai San Cheang.,Wing Tak Wong.,Lei Zhao.,Jian Xu.,Li Wang.,...&Yu Huang.(2017).PPARδ is required for exercise to attenuate endoplasmic reticulum stress and endothelial dysfunction in diabetic mice.DIABETES,66(2),519-528.
MLA Wai San Cheang,et al."PPARδ is required for exercise to attenuate endoplasmic reticulum stress and endothelial dysfunction in diabetic mice".DIABETES 66.2(2017):519-528.
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